Neonatal polyI:C treatment in mice results in schizophrenia-like behavioral and neurochemical abnormalities in adulthood
Neonatal polyI:C treatment in mice results in schizophrenia-like behavioral and neurochemical abnormalities in adulthood
复制标题
DOI：
10.1016/j.neures.2009.03.015
复制
发表时间：
2009-07-01
影响因子：
2.9
通讯作者：
Yamada, Kiyofumi
中科院分区：
文献类型：
--
作者：
Ibi, Daisuke;Nagai, Taku;Yamada, Kiyofumi
据报道，人类在怀孕的第一个和第二个三个月的病毒感染增加了随后发展为精神分裂症的风险。为了开发出生后早期免疫激活的小鼠模型，新生ICR小鼠重复注射多聚核糖肌苷酸-多聚核糖胞苷酸（polyI：C：强先天免疫应答的诱导剂）5天（出生后第2-6天），这在脑发育方面可能对应于人类的早期中期妊娠。在10-12周龄时分析认知和情绪行为以及海马细胞外谷氨酸水平。与生理盐水处理的对照组相比，PolyI：C处理的小鼠表现出焦虑样行为、物体识别记忆和社会行为受损以及感觉运动门控缺陷。去极化诱发的谷氨酸释放在海马受损polyI：C处理的小鼠相比，盐水处理的对照组小鼠。此外，研究新生儿免疫激活对精神分裂症相关基因表达水平的影响，我们分析了海马mRNA水平2和24小时后聚乙二醇：C治疗。没有显着差异或只有短暂的和边缘的变化，观察聚乙二醇：C-处理和盐水处理的对照小鼠在海马中的精神分裂症相关基因的表达水平。(c)2009年爱思唯尔爱尔兰有限公司和日本神经科学学会。All rights reserved.
It has been reported that viral infection in the first and second trimesters of pregnancy in humans increases the risk of subsequently developing schizophrenia. To develop a mouse model of immune activation during the early postnatal period, neonatal ICR mice were repeatedly injected with polyriboinosinic-polyribocytidilic acid (polyI:C: an inducer of strong innate immune responses) for 5 days (postnatal day 2-6) which may correspond, in terms of brain development, to the early second trimester in human. Cognitive and emotional behavior as well as the extracellular level of glutamate in the hippocampus were analyzed at the age of 10-12 weeks old. PolyI:C-treated mice showed anxiety-like behavior, impairment of object recognition memory and social behavior, and sensorimotor gating deficits, as compared to the saline-treated control group. Depolarization-evoked glutamate release in the hippocampus was impaired in polyI:C-treated mice compared to saline-treated control mice. Furthermore, to investigate the effect of neonatal immune activation on the expression levels of schizophrenia-related genes, we analyzed mRNA levels in the hippocampus 2 and 24 h after polyl:C treatment. No significant differences or only transient and marginal changes were observed between polyl:C-treated and saline-treated control mice in the expression levels of schizophrenia-related genes in the hippocampus. (c) 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.